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Matsui H, Ioka T, Kawaoka T, Takahashi T, Inokuchi T, Harada E, Sakamoto K, Suto R, Maeda Y, Nishimura T, Shindo Y, Tokumitsu Y, Nakajima M, Kimura Y, Takami T, Ito K, Tanaka H, Hamano K, Nagano H, Yamaguchi Pancreatic/Biliary Disease Study Group (YPB). Survival Analysis of 4 Different Age Groups of Pancreatic Ductal Adenocarcinoma After Radical Resection From Retrospective Multi-Center Analysis (YPB-003). Cancer Med 2025; 14:e70647. [PMID: 39950748 PMCID: PMC11826832 DOI: 10.1002/cam4.70647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 12/10/2024] [Accepted: 01/23/2025] [Indexed: 02/17/2025] Open
Abstract
AIM This study aimed to investigate the efficacy of radical resection and postoperative adjuvant chemotherapy on the survival benefit in patients with pancreatic ductal adenocarcinoma (PDAC), stratified by age, frailty, and other factors in actual clinical practice. METHODS We retrospectively analyzed the clinicopathological and follow-up data of 414 patients with PDAC who underwent surgical resection at nine institutions under the Yamaguchi Pancreat/Biliary Disease Study Group, between January 1997 and December 2016. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Associations between survival and prognostic factors were evaluated by univariate and multivariate analyses. RESULTS There were 30.5% of patients with PDAC who were aged < 65 years, 37.9% aged 65-74 years, 17.6% aged 75-79 years, and 14.0% aged ≥ 80 years. Notably, RFS declined with increasing age (median RFS: 12.9, 10.2, 9.4, and 7.4 months, respectively), although the differences were not significant (p = 0.223). OS significantly decreased with age (median OS: 21.6, 21.2, 17.0, and 13.9 months, respectively; p = 0.005). In patients aged < 75 years, independent prognostic factors identified by univariate and multivariate analyses included lymph node metastasis (hazard ratio [HR], 1.598; p = 0.007), tumor size (HR, 1.489; p = 0.043), R status (HR, 1.536; p = 0.011), and serum albumin levels (HR, 1.526; p = 0.031). In patients aged ≥ 75 years, a high modified frailty index (HR, 2.446; p = 0.012) emerged as an independent prognostic factor, along with lymph node metastasis, CA19-9 level (HR, 1.897; p = 0.017), and R status (HR, 2.087; p = 0.007). CONCLUSION The prognosis for older patients with PDAC was shorter than that of younger patients. Frailty may contribute to their poorer prognosis in older age.
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Affiliation(s)
- Hiroto Matsui
- Department of GastroenterologicalBreast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine UbeYamaguchiJapan
| | - Tatsuya Ioka
- Yamaguchi University Hospital Cancer Center UbeYamaguchiJapan
| | - Toru Kawaoka
- Department of SurgeryTokuyama Central HospitalTokuyamaJapan
| | | | | | - Eijiro Harada
- Department of Surgery and Clinical ScienceYamaguchi University Graduate School of MedicineUbeJapan
| | | | - Ryuichiro Suto
- Department of SurgeryYamaguchi Prefectural Grand Medical CenterHofuJapan
| | | | - Taku Nishimura
- Department of Gastroenterological SurgeryJCHO Shimonoseki Medical CenterShimonosekiJapan
| | - Yoshitaro Shindo
- Department of GastroenterologicalBreast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine UbeYamaguchiJapan
| | - Yukio Tokumitsu
- Department of GastroenterologicalBreast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine UbeYamaguchiJapan
| | - Masao Nakajima
- Department of GastroenterologicalBreast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine UbeYamaguchiJapan
| | - Yuta Kimura
- Department of GastroenterologicalBreast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine UbeYamaguchiJapan
| | - Taro Takami
- Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Katsuyoshi Ito
- Department of RadiologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Hidekazu Tanaka
- Department of Radiation OncologyYamaguchi University Graduate School of MedicineUbeJapan
| | - Kimikazu Hamano
- Department of Surgery and Clinical ScienceYamaguchi University Graduate School of MedicineUbeJapan
| | - Hiroaki Nagano
- Department of GastroenterologicalBreast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine UbeYamaguchiJapan
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Gupta R, Das CK, Nair SS, Pedraza-Bermeo AM, Zahalka AH, Kyprianou N, Bhardwaj N, Tewari AK. From foes to friends: rethinking the role of lymph nodes in prostate cancer. Nat Rev Urol 2024; 21:687-700. [PMID: 39095580 DOI: 10.1038/s41585-024-00912-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2024] [Indexed: 08/04/2024]
Abstract
Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly 'foes' or whether they are actually 'friends' in oncological care is an important idea to discuss.
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Affiliation(s)
- Raghav Gupta
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Chandan K Das
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sujit S Nair
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Ali H Zahalka
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Natasha Kyprianou
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Nina Bhardwaj
- Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ashutosh K Tewari
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1724-1785. [PMID: 39389105 DOI: 10.1055/a-2338-3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:874-995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Uemura K, Kondo N, Sudo T, Sumiyoshi T, Shintakuya R, Okada K, Baba K, Harada T, Murakami Y, Takahashi S. Long-term outcomes of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact: Results from a phase II trial. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2024; 31:351-362. [PMID: 38156372 DOI: 10.1002/jhbp.1412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/10/2023] [Accepted: 12/01/2023] [Indexed: 12/30/2023]
Abstract
BACKGROUND/PURPOSE This study reports the long-term results of a phase II trial evaluating the clinical efficacy of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact (BRPC-A). METHODS A multicenter, single-arm, phase II trial was conducted. Patients received six cycles of GAS and patients without progressive disease were intended for R0 resection. RESULTS Of the 47 patients, 45 (96%) underwent pancreatectomy. At the time of this analysis, all patients were updated with no loss to follow-up. A total of 30 patients died, while the remaining 17 patients were followed for a median of 68.1 months. The updated median overall survival (OS) was 41.0 months, with 2- and 5-year OS rates of 68.0% and 44.6%, respectively. Multivariate analysis in the preoperative model showed that a tumor diameter reduction rate ≥10% and a CA19-9 reduction rate ≥95% after neoadjuvant chemotherapy remained independently associated with favorable survival. In the postoperative multivariate model, no lymph node metastasis, no major surgical complications, and completion of adjuvant chemotherapy were independently associated with improved OS. CONCLUSIONS This long-term evaluation of the neoadjuvant GAS trial demonstrated the high efficacy of the regimen, suggesting that it is a promising treatment option for patients with BRPC-A.
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Affiliation(s)
- Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takeshi Sudo
- Department of Surgery, Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryuta Shintakuya
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kenta Baba
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takumi Harada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Abe S, Nakai Y, Arita J, Ichida A, Kawaguchi Y, Akamatsu N, Kaneko J, Ijichi H, Koike K, Fujishiro M, Hasegawa K. The Effect of Renin-Angiotensin System Inhibitors in Patients Undergoing Pancreatic Cancer Resection. Pancreas 2024; 53:e233-e239. [PMID: 38227640 DOI: 10.1097/mpa.0000000000002291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
OBJECTIVES The local renin-angiotensin system promotes angiogenesis and proliferation via vascular endothelial growth factor or epidermal growth factor receptor expression. In this study, we aimed to evaluate the impact of angiotensin system inhibitors (ASIs) on long-term outcomes in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). METHODS A single institutional retrospective analysis was performed using the medical records of patients who underwent pancreatic resection with curative intent for PDAC between January 2005 and December 2018. Patient characteristics and surgical outcomes were compared between patients taking ASIs and those who are not. RESULTS A total of 272 patients were included in the study and classified into the ASI group (n = 121) and the non-ASI group (n = 151). The median overall survival times in the ASI group and non-ASI group were 38.0 and 34.0 months ( P = 0.250), and the median recurrence-free survival times were 24.0 and 15.0 months ( P = 0.025), respectively. Multivariate analysis for recurrence-free survival identified the use of ASIs ( P = 0.020), CA19-9 level >500 IU/L ( P = 0.010), positive lymph node metastasis ( P < 0.001), and no adjuvant chemotherapy ( P < 0.001) as independent prognostic factors. CONCLUSIONS The use of ASI may improve long-term outcomes after surgery for PDAC.
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Affiliation(s)
- Satoru Abe
- From the Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- From the Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery
| | - Akihiko Ichida
- From the Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery
| | - Yoshikuni Kawaguchi
- From the Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery
| | - Nobuhisa Akamatsu
- From the Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery
| | - Junichi Kaneko
- From the Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery
| | - Hideaki Ijichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- From the Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery
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Xie N, Fan X, Chen D, Chen J, Yu H, He M, Liu H, Yin X, Li B, Wang H. Peritumoral and Intratumoral Texture Features Based on Multiparametric MRI and Multiple Machine Learning Methods to Preoperatively Evaluate the Pathological Outcomes of Pancreatic Cancer. J Magn Reson Imaging 2023; 58:379-391. [PMID: 36426965 DOI: 10.1002/jmri.28538] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/13/2022] [Accepted: 11/14/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Radiomics-based preoperative evaluation of lymph node metastasis (LNM) and histological grade (HG) might facilitate the decision-making for pancreatic cancer and further efforts are needed to develop effective models. PURPOSE To develop multiparametric MRI (MP-MRI)-based radiomics models to evaluate LNM and HG. STUDY TYPE Retrospective. POPULATION The pancreatic cancer patients from the main center (n = 126) were assigned to the training and validation sets at a 4:1 ratio. The patients from the other center (n = 40) served as external test sets. FIELD STRENGTH/SEQUENCE A 3.0 T and 1.5 T/T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement T1-weighted imaging. ASSESSMENT A total of 10,686 peritumoral and intratumoral radiomics features were extracted which contained first-order, shape-based, and texture features. The following three-step method was applied to reduce the feature dimensionality: SelectKBest (a function from scikit-learn package), least absolute shrinkage and selection operator (LASSO), and recursive feature elimination based on random forest (RFE-RF). Six classifiers (random forest, logistic regression, support vector machine, K-nearest neighbor, decision tree, and XGBOOST) were trained and selected based on their performance to construct the clinical, radiomics, and combination models. STATISTICAL TESTS Delong's test was used to compare the models' performance. P value less than 0.05 was considered significant. RESULTS Twelve significant features for LNM and 11 features for HG were obtained. Random forest and logistic regression performed better than the other classifiers in evaluating LNM and HG, respectively, according to the surgical pathological results. The best performance was obtained with the models that combined peritumoral and intratumoral features with area under curve (AUC) values of 0.944 and 0.892 in the validation and external test sets for HG and 0.924 and 0.875 for LNM. DATA CONCLUSION Radiomics holds the potential to evaluate LNM and HG of pancreatic cancer. The combination of peritumoral and intratumoral features will make models more accurate. EVIDENCE LEVEL 4. TECHNICAL EFFICACY Stage 2.
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Affiliation(s)
- Ni Xie
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuhui Fan
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Desheng Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingwen Chen
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Hongwei Yu
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Meijuan He
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
| | - Hao Liu
- Yizhun Medical AI Technology Co. Ltd., Beijing, China
| | - Xiaorui Yin
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
| | - Baiwen Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Han Wang
- Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- R & D Center of Medical Artificial Intelligence and Medical Engineering, Shanghai General Hospital, Shanghai, China
- National Center for Translational Medicine (Shanghai), Shanghai, China
- Jiading Branch of Shanghai General Hospital, Shanghai, China
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Granieri S, Kersik A, Bonomi A, Frassini S, Bernasconi D, Paleino S, Germini A, Gjoni E, Cotsoglou C. The Role of Non-Peripancreatic Lymph Nodes in the Survival of Patients Suffering from Pancreatic Cancer of the Body and Tail: A Systematic Review and Meta-Analysis of High-Quality Studies. Cancers (Basel) 2023; 15:cancers15082322. [PMID: 37190250 DOI: 10.3390/cancers15082322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/12/2023] [Accepted: 04/13/2023] [Indexed: 05/17/2023] Open
Abstract
Lymph nodes (LNs)' metastases have a well-known detrimental impact on the survival outcomes of patients suffering from pancreatic cancer of the body and tail. However, the extent of the lymphadenectomy for this tumor location is still debated. The aim of this study was to systematically review the current literature to explore the incidence and the prognostic impact of non-peripancreatic lymph nodes (PLNs) in patients suffering from pancreatic cancer of the body and tail. A systematic review was conducted according to PRISMA and MOOSE guidelines. The primary endpoint was to assess the impact of non-PLNs on overall survival (OS). As a secondary endpoint, the pooled frequencies of different non-PLN stations' metastatic patterns according to tumor location were explored. Eight studies were included in data synthesis. An increased risk of death for patients with positive non-PLNs was detected (HR: 2.97; 95% CI: 1.81-4.91; p < 0.0001). Meta-analysis of proportions pointed out a 7.1% pooled proportion of nodal infiltration in stations 8-9. The pooled frequency for station 12 metastasis was 4.8%. LN stations 14-15 were involved in 11.4% of cases, whereas station 16 represented a site of metastasis in 11.5% of cases. Despite its potential beneficial effect on survival outcome, a systematic extended lymphadenectomy could not be recommended yet for patients suffering from PDAC of the body/tail.
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Affiliation(s)
- Stefano Granieri
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Alessia Kersik
- General Surgery Residency Program, University of Milan, Via Festa del Perdono, 7, 20122 Milan, Italy
| | - Alessandro Bonomi
- General Surgery Residency Program, University of Milan, Via Festa del Perdono, 7, 20122 Milan, Italy
| | - Simone Frassini
- General Surgery Residency Program, University of Pavia, Corso Str. Nuova, 65, 27100 Pavia, Italy
- General Surgery Unit, Department of Surgery, Fondazione I.R.C.C.S. Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy
| | - Davide Bernasconi
- Center of Biostatistics for Clinical Epidemiology, University of Milan-Bicocca, Via Cadore, 48, 20854 Monza, Italy
| | - Sissi Paleino
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Alessandro Germini
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Elson Gjoni
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
| | - Christian Cotsoglou
- General Surgery Unit, ASST-Brianza, Vimercate Hospital, Via Santi Cosma e Damiano, 10, 20871 Vimercate, Italy
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Kado T, Tomimaru Y, Kobayashi S, Takahashi H, Sasaki K, Iwagami Y, Yamada D, Noda T, Doki Y, Eguchi H. Prognostic Impact of Gastroduodenal Artery Involvement in Cancer of the Pancreatic Head. Ann Surg Oncol 2023; 30:2413-2421. [PMID: 36372849 DOI: 10.1245/s10434-022-12759-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/17/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) contacting major arteries such as the celiac, common hepatic, and superior mesenteric artery is linked to poor prognosis and classified as borderline resectable. Although PDAC involving the gastroduodenal artery (GDA) is considered resectable, the prognostic impact of GDA involvement remains unclear. Here we investigated the prognostic impact of GDA involvement in PDAC after resection. METHODS This study included 105 patients with resectable PDAC or borderline resectable with portal vein involvement. Patients were divided into two groups: those with tumor-GDA contact ≤ 180° and those with GDA contact > 180°. We evaluated the prognostic impact of GDA involvement between these groups. RESULTS Both recurrence-free and overall survival after the surgery were significantly poorer with GDA contact > 180° than ≤ 180°. The poorer prognosis with GDA contact > 180° was verified by multivariate analysis and propensity score matching analysis to match patient backgrounds between the groups. The frequency of postoperative distant metastasis was also significantly higher in patients with GDA contact > 180°. CONCLUSIONS GDA involvement is an independent factor significantly associated with postoperative survival in PDAC, and the poorer prognosis with GDA involvement may be linked to the development of postoperative distant metastasis.
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Affiliation(s)
- Takeshi Kado
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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A Lymph Node Ratio Model for Prognosis of Patients with Pancreatic Neuroendocrine Tumors. Biomedicines 2023; 11:biomedicines11020407. [PMID: 36830943 PMCID: PMC9953747 DOI: 10.3390/biomedicines11020407] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/17/2023] [Accepted: 01/22/2023] [Indexed: 01/31/2023] Open
Abstract
The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS p = 0.002 HR = 13.4 and 5-year DFS p = 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS p = 0.004 HR = 9 and p = 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.
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11
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Matsui Y, Hashimoto D, Satoi S, Yamamoto T, Yamaki S, Ishida M, Hirooka S, Ikeura T, Sekimoto M. Reevaluation of regional lymph nodes in patients with pancreatic ductal adenocarcinoma in the pancreatic body and tail. Ann Gastroenterol Surg 2023; 7:147-156. [PMID: 36643361 PMCID: PMC9831907 DOI: 10.1002/ags3.12608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/16/2022] [Indexed: 01/18/2023] Open
Abstract
Introduction In patients with pancreatic ductal adenocarcinoma (PDAC) in the pancreatic body (Pb) and tail (Pt), the appropriate area for lymphadenectomy is controversial. This study aimed to reevaluate the extent of lymph node (LN) metastasis in Pb- and Pt-PDAC, and to define the optimal area of LN dissection. Patients and methods This single-center retrospective study evaluated patients with Pb- and Pt-PDAC who underwent distal pancreatectomy with extended lymphadenectomy between 2006 and 2020. LN metastasis in >3.0% of patients were defined as new regional LN. Results The study cohort included 135 patients with Pb-PDAC and 42 patients with Pt-PDAC. In patients with Pb-PDAC, LNs around the splenic artery (SPA) had the highest metastasis-positive rate (54.1%). LNs along the left gastric artery, common hepatic artery, celiac axis (CA), superior mesenteric artery (SMA), and splenic hilus were defined as new regional LNs. In patients with Pt-PDAC, LNs at the splenic hilum had the highest metastasis-positive rate (38.1%). The station and LN around the SPA were defined as new regional LNs in those with Pt-PDAC. Metastasis beyond the newly defined regional LNs was not associated with survival. The incidence of LN metastasis was lower in patients who received preoperative chemotherapy than in those who underwent upfront surgery in both Pb- and Pt-PDAC. Conclusion Although it needs to be verified in future multicenter studies, LN of both the CA and SMA systems should be dissected in patients with Pb-PDAC. However, only those around the SPA and splenic hilus should be dissected routinely in those with Pt-PDAC.
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Affiliation(s)
- Yuki Matsui
- Department of SurgeryKansai Medical UniversityOsakaJapan
| | | | - Sohei Satoi
- Department of SurgeryKansai Medical UniversityOsakaJapan
- Division of Surgical OncologyUniversity of Colorado Anschutz Medical CampusAuroraColoradoUSA
| | | | - So Yamaki
- Department of SurgeryKansai Medical UniversityOsakaJapan
| | - Mitsuaki Ishida
- Department of PathologyOsaka Medical and Pharmaceutical UniversityOsakaJapan
| | | | - Tsukasa Ikeura
- Third Department of Internal MedicineKansai Medical UniversityOsakaJapan
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12
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Nassoiy S, Christopher W, Marcus R, Keller J, Weiss J, Chang SC, Essner R, Foshag L, Fischer T, Goldfarb M. Evolving management of early stage pancreatic adenocarcinoma in older patients. Am J Surg 2023; 225:212-219. [PMID: 36058752 DOI: 10.1016/j.amjsurg.2022.07.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Due to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise. STUDY DESIGN Utilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death. RESULTS Of 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT. CONCLUSION For older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.
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Affiliation(s)
- Sean Nassoiy
- Providence St. John's Cancer Institute, Santa Monica, CA, USA
| | | | - Rebecca Marcus
- Providence St. John's Cancer Institute, Santa Monica, CA, USA
| | - Jennifer Keller
- Providence St. John's Cancer Institute, Santa Monica, CA, USA
| | - Jessica Weiss
- Providence St. John's Cancer Institute, Santa Monica, CA, USA
| | | | - Richard Essner
- Providence St. John's Cancer Institute, Santa Monica, CA, USA
| | - Leland Foshag
- Providence St. John's Cancer Institute, Santa Monica, CA, USA
| | - Trevan Fischer
- Providence St. John's Cancer Institute, Santa Monica, CA, USA
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13
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Langversion 2.0 – Dezember 2021 – AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e812-e909. [PMID: 36368658 DOI: 10.1055/a-1856-7346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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14
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Malleo G, Maggino L, Qadan M, Marchegiani G, Ferrone CR, Paiella S, Luchini C, Mino-Kenudson M, Capelli P, Scarpa A, Lillemoe KD, Bassi C, Castillo CFD, Salvia R. Reassessment of the Optimal Number of Examined Lymph Nodes in Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma. Ann Surg 2022; 276:e518-e526. [PMID: 33177357 DOI: 10.1097/sla.0000000000004552] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of this study was to reappraise the optimal number of examined lymph nodes (ELNs) in pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA The well-established threshold of 15 ELNs in PD for PDAC is optimized for detecting 1 positive node (PLN) per the previous 7th edition of the American Joint Committee on Cancer (AJCC) staging manual. In the framework of the 8th edition, where at least 4 PLN are needed for an N2 diagnosis, this threshold may be inadequate for accurate staging. METHODS Patients who underwent upfront PD at 2 academic institutions between 2000 and 2016 were analyzed. The optimal ELN threshold was defined as the cut-point associated with a 95% probability of identifying at least 4 PLNs in N2 patients. The results were validated addressing the N-status distribution and stage migration. RESULTS Overall, 1218 patients were included. The median number of ELN was 26 (IQR 17-37). ELN was independently associated with N2-status (OR 1.27, P < 0.001). The estimated optimal threshold of ELN was 28. This cut-point enabled improved detection of N2 patients and stage III disease (58% vs 37%, P = 0.001). The median survival was 28.6 months. There was an improved survival in N0/N1 patients when ELN exceeded 28, suggesting a stage migration effect (47 vs 29 months, adjusted HR 0.649, P < 0.001). In N2 patients, this threshold was not associated with survival on multivariable analysis. CONCLUSION Examining at least 28 LN in PD for PDAC ensures optimal staging through improved detection of N2/stage III disease. This may have relevant implications for benchmarking processes and quality implementation.
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Affiliation(s)
- Giuseppe Malleo
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Laura Maggino
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Giovanni Marchegiani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Salvatore Paiella
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Luchini
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Paola Capelli
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Aldo Scarpa
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | | | - Roberto Salvia
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
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Kang H, Kim SS, Sung MJ, Jo JH, Lee HS, Chung MJ, Park JY, Park SW, Song SY, Park MS, Bang S. Evaluation of the 8th Edition AJCC Staging System for the Clinical Staging of Pancreatic Cancer. Cancers (Basel) 2022; 14:4672. [PMID: 36230595 PMCID: PMC9563770 DOI: 10.3390/cancers14194672] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/15/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.
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Affiliation(s)
- Huapyong Kang
- Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Korea
- Department of Medicine, Yonsei University Graduate School, Seoul 03722, Korea
| | - Seung-seob Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Min Je Sung
- Digestive Disease Center, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Korea
| | - Jung Hyun Jo
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Si Young Song
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Mi-Suk Park
- Department of Radiology, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
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16
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Barrak D, Villano AM, Moslim MA, Hopkins SE, Lefton MD, Ruth K, Reddy SS. Total Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma Is Associated With Limited Lymph Node Yield but Improved Ratio. J Surg Res 2022; 280:543-550. [PMID: 36096019 DOI: 10.1016/j.jss.2022.08.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 07/09/2022] [Accepted: 08/16/2022] [Indexed: 10/14/2022]
Abstract
INTRODUCTION The lymph node yield (LNY) and lymph node ratio (LNR) of nodal metastases following pancreatoduodenectomy (PD) have been reported as prognostic parameters in patients with pancreatic ductal adenocarcinoma (PDAC). However, they have not been compared in the setting of various neoadjuvant therapy modalities. METHODS A single institutional retrospective study identified 134 patients diagnosed with resectable, BLR- and LA-PDAC who underwent PD at Fox Chase Cancer Center between 2010 and 2019. Patients were categorized based on first-line treatment as follows: surgery first (SF), total neoadjuvant therapy (TNT), and single modality neoadjuvant therapy (SMNT). The histopathological reports of the surgical specimens were examined to obtain LNY and determine the counts of lymph nodes with metastases. Subsequently, LNR was calculated as the number of positive lymph nodes divided by the number of lymph nodes examined. RESULTS Overall, 49, 38, 27, 12, and 8 patients underwent SF approach, SMNT, incomplete TNT, induction TNT, and consolidation TNT, respectively. There was no difference in R0 resection and vascular resection between the groups (P = 0.096 and 0.794, respectively). The median counts of LNY were 22, 15, 21, 11.5, and 10, respectively (P < 0.001). The average LNR was 0.16, 0.07, 0.03, 0.02, and 0.02, respectively (P < 0.001). There were statistically significant differences in overall survival in the TNT groups (log-rank test P = 0.030). CONCLUSIONS PDAC patients who undergo the TNT modality exhibit lower LNY and improved LNR compared with the SF approach and SMNT neoadjuvant therapy groups. This is likely explained by the increased treatment response and lymph node obliteration associated with the TNT approach. Our results question the minimal requirement of 11-18 harvested lymph nodes for PD following TNT.
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Affiliation(s)
- Dany Barrak
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Anthony M Villano
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Maitham A Moslim
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Steven E Hopkins
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Max D Lefton
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Karen Ruth
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Sanjay S Reddy
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
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17
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Min SK, You Y, Choi DW, Han IW, Shin SH, Yoon S, Jung JH, Yoon SJ, Heo JS. Prognosis of pancreatic head cancer with different patterns of lymph node metastasis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:1004-1013. [PMID: 35446462 DOI: 10.1002/jhbp.1159] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/19/2022] [Accepted: 03/27/2022] [Indexed: 11/11/2022]
Abstract
BACKGROUND The nodal stage of pancreatic ductal adenocarcinoma (PDAC) is revised in the AJCC 8th edition. Studies on the prognosis of PDAC according to lymph node metastasis (LNM) are still ongoing. We attempted to find the patterns of nodal involvement and to reveal its clinical significance to overall survival (OS). METHODS We analyzed 585 patients who received pancreatic head cancer surgery diagnosed as PDAC from January 2007 to December 2016. Patients were classified into three groups: Group 1 (G1, patients without LNM), Group 2 (G2, those with LNM only in the peripancreatic area), and Group 3 (G3 those with LNM in the other area and/or peripancreatic LNM). Risk factors were analyzed by Cox-regression test and overall survival was compared by Kaplan-Meier analysis. RESULTS LNM in peripancreatic area was the most common (88.7%). In the multivariate analysis, T stage, nuclear differentiation, adjuvant treatment, and the G2 and G3 were independent risk factors for OS (G2 over G1, HR 1.384, 95% CI 1.046-1.802; P = .036 and G3 over G1, HR 2.383, 95% CI 1.378-4.103; P = .001). G3 showed worse OS than G2 (P = .006). In the N1 status, LNM to the pericholedochal (PC) and superior mesenteric artery (SMA) areas resulted in worse OS than the G2 (P = .011 and P = .019). CONCLUSIONS We found that LNM beyond the peripancreatic area significantly affects OS in pancreatic head cancer patients. Depending on the station of the LNM, different risk-stratification and treatment strategies will need to be considered.
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Affiliation(s)
- Seung Ki Min
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yunghun You
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Wook Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In Woong Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Hyun Shin
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sokyung Yoon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Ji Hye Jung
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - So Jeong Yoon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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18
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Schouten TJ, Daamen LA, Dorland G, van Roessel SR, Groot VP, Besselink MG, Bonsing BA, Bosscha K, Brosens LAA, Busch OR, van Dam RM, Fariña Sarasqueta A, Festen S, Groot Koerkamp B, van der Harst E, de Hingh IHJT, Intven M, Kazemier G, de Meijer VE, Nieuwenhuijs VB, Raicu GM, Roos D, Schreinemakers JMJ, Stommel MWJ, van Velthuysen MF, Verdonk RC, Verheij J, Verkooijen HM, van Santvoort HC, Molenaar IQ, The Dutch Pancreatic Cancer Group. Nationwide Validation of the 8th American Joint Committee on Cancer TNM Staging System and Five Proposed Modifications for Resected Pancreatic Cancer. Ann Surg Oncol 2022; 29:5988-5999. [PMID: 35469113 PMCID: PMC9356941 DOI: 10.1245/s10434-022-11664-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 03/06/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five proposed modifications. METHODS Patients who underwent pancreatic ductal adenocarcinoma resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan-Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS). RESULTS Overall, 750 patients with a median OS of 18 months (interquartile range 10-32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval [CI] 0.56-0.61) vs. 0.56 (95% CI 0.54-0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio [HR] 1.30, 95% CI 0.80-2.09; p = 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75-1.83; p = 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59-0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (p < 0.05). CONCLUSIONS The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.
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Affiliation(s)
- Thijs J. Schouten
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Lois A. Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands
| | - Galina Dorland
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Stijn R. van Roessel
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Vincent P. Groot
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Marc G. Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bert A. Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Koop Bosscha
- Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | | | - Olivier R. Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Ronald M. van Dam
- Department of Surgery, Maastricht UMC+, Maastricht, The Netherlands
- GROW - School for Oncology & Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of General and Visceral Surgery, University Hospital Aachen, Aachen, Germany
| | - Arantza Fariña Sarasqueta
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | | | | | | | - Ignace H. J. T. de Hingh
- GROW - School for Oncology & Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Martijn Intven
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center, Amsterdam, The Netherlands
| | - Vincent E. de Meijer
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | | | - G. Mihaela Raicu
- Department of Pathology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Daphne Roos
- Department of Surgery, Reinier de Graaf Group, Delft, The Netherlands
| | | | | | | | - Robert C. Verdonk
- Department of Gastroenterology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Helena M. Verkooijen
- Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands
- Utrecht University, Utrecht, The Netherlands
| | - Hjalmar C. van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - I. Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - The Dutch Pancreatic Cancer Group
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
- Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands
- Department of Pathology, UMC Utrecht Cancer Center, Utrecht, The Netherlands
- Department of Surgery, Maastricht UMC+, Maastricht, The Netherlands
- GROW - School for Oncology & Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of General and Visceral Surgery, University Hospital Aachen, Aachen, Germany
- Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, OLVG, Amsterdam, The Netherlands
- Department of Surgery, Erasmus MC, Rotterdam, The Netherlands
- Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center, Amsterdam, The Netherlands
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
- Department of Surgery, Isala, Zwolle, The Netherlands
- Department of Pathology, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Surgery, Reinier de Graaf Group, Delft, The Netherlands
- Department of Surgery, Amphia Hospital, Breda, The Netherlands
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Pathology, Erasmus MC, Rotterdam, Netherlands
- Department of Gastroenterology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
- Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands
- Utrecht University, Utrecht, The Netherlands
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Seo S, Uemura K, Sumiyoshi T, Kondo N, Okada K, Otsuka H, Murakami Y, Takahashi S. Optimal lymph-node dissection for pancreatic tail cancer. Surg Today 2022; 52:1307-1312. [PMID: 35182251 DOI: 10.1007/s00595-022-02463-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 12/05/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE The optimal range of lymph-node dissection for pancreatic tail cancer remains unclear. We investigated the location and frequency of lymph-node metastases to identify the correct range of lymph-node dissection for pancreatic tail cancer. METHODS We analyzed clinical data retrospectively, on patients who underwent distal pancreatectomy for resectable left-sided pancreatic cancer, between February, 2006 and March, 2021. Eligible patients were divided into two groups according to the tumor location: those with pancreatic tail cancer (Pt group) and those with pancreatic body or body and tail cancer (non-Pt group). RESULTS Of the 96 patients analyzed, 61 (64%) were assigned to the Pt group and 35 (36%) were assigned to the non-Pt group. Metastases to stations 7, 8, 9, 10, 11, 14, and 18 were found in 0 (0%), 0 (0%), 0 (0%), 4 (7%), 18 (30%), 2 (4%), and 10 (17%) patients in the Pt group, and in 1 (3%), 4 (12%), 2 (6%), 1 (3%), 18 (51%), 3 (9%), and 6 (17%) patients in the non-Pt group, respectively. CONCLUSION Lymph-node dissection at stations 7, 8, and 9 might not be necessary in patients with resectable pancreatic cancer confined to the pancreatic tail.
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Affiliation(s)
- Shingo Seo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yoshiaki Murakami
- Digestive Disease Center, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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20
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Minagawa T, Sugiura T, Okamura Y, Ito T, Yamamoto Y, Ashida R, Ohgi K, Sasaki K, Uesaka K. Clinical implications of lymphadenectomy for invasive ductal carcinoma of the body or tail of the pancreas. Ann Gastroenterol Surg 2022; 6:531-542. [PMID: 35847444 PMCID: PMC9271019 DOI: 10.1002/ags3.12551] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/16/2021] [Accepted: 01/05/2022] [Indexed: 01/23/2023] Open
Abstract
Aim The appropriate extent of lymphadenectomy for pancreatic cancer of the body/tail has not been standardized worldwide. The present study evaluated the optimal extent of harvesting lymph nodes. Methods Patients who underwent distal pancreatectomy for invasive ductal carcinoma of the pancreas between 2007 and 2018 were retrospectively reviewed. Patients were subclassified into three groups depending on the tumor location: pancreatic body (Pb), proximal pancreatic tail (Ptp), and distal pancreatic tail (Ptd). The pancreatic tail was further divided into even sections of Ptp and Ptd. Patterns of lymph node metastasis and the impact of lymph node metastasis on the prognosis were examined. Results A total of 120 patients were evaluated. Fifty-eight patients had a tumor in the Pb, 38 in the Ptp, and 24 in the Ptd. No patients with a Ptd tumor had metastasis beyond the peripancreatic and splenic hilar lymph nodes (LN-PSH). All patients with metastasis to the lymph nodes along the common hepatic artery (LN-CHA) or along the left lateral superior mesenteric artery (LN-SMA) also had metastasis to the LN-PSH. Recurrence after surgery occurred significantly earlier in this population. In a multivariate analysis, metastasis to the LN-CHA or LN-SMA (hazard ratio [HR] 3.3; P = .04) was an independent risk factor for overall survival. Furthermore, high levels of preoperative serum CA19-9 (HR 10.9; P = .013) were a predictive factor for metastasis to the LN-CHA or LN-SMA. Conclusions Metastasis to the LN-CHA or LN-SMA was rare but a significant prognostic factor in patients with pancreatic body/tail cancer.
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Affiliation(s)
- Takuya Minagawa
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Teiichi Sugiura
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Yukiyasu Okamura
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Takaaki Ito
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Yusuke Yamamoto
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Ryo Ashida
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Katsuhisa Ohgi
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
| | - Keiko Sasaki
- Division of PathologyShizuoka Cancer CenterShizuokaJapan
| | - Katsuhiko Uesaka
- Division of Hepato‐Biliary‐Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
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21
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Kurzversion 2.0 – Dezember 2021, AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:991-1037. [PMID: 35671996 DOI: 10.1055/a-1771-6811] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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22
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Lee W, Lee JB, Hong S, Park Y, Kwak BJ, Jun E, Song KB, Lee JH, Hwang DW, Kim SC. Predictive Performance of Current Nodal Staging Systems in Various Categories of Pancreatic Cancer. Ann Surg Oncol 2022; 29:390-398. [PMID: 34423402 DOI: 10.1245/s10434-021-10641-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 07/24/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Nodal staging systems (NSS) for pancreatic ductal adenocarcinoma (PDAC) classify patients on the basis of number of metastatic lymph nodes (MLN), metastatic/retrieved lymph node ratio (LNR), and log odds of positive LN (LODDS). The relative prognostic performance of these NSS, however, remains unclear. PATIENTS AND METHODS We identified 2584 patients who underwent surgery for PDAC between 2010 and 2019. Subgroups of each staging system were classified using K-adaptive partitioning method and assessed by comparing time-dependent areas under the curve (AUC) 5 years after surgery. RESULTS Patients were subgrouped by MLN (0, 1-3, ≥ 4), LNR (0, 0-0.23, > 0.23), and LODDS (< - 3.5, - 3.5 to - 0.970, > - 0.97). All three NSS were independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS). The AUCs for OS were comparable for the MLN (0.622), LNR (0.609), and LODDS (0.596) systems. Subgroup evaluation based on 12 retrieved lymph nodes (RLN), R1 resection, and extent of resection showed that the AUCs of the MLN and LNR NSS were comparable for OS and RFS regardless of the number of RLNs, R1 resection, and extent of resection. By contrast, the AUCs of the LODDS NSS were lower. CONCLUSION The NSS based on the number of MLN is the best prognostic indicator, with prognostic performance comparable to the other NSS and greater convenience for practical use. This NSS was applicable regardless of the numbers of RLN, R1 resection, and extent of resection.
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Affiliation(s)
- Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Jung Bok Lee
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Bong Jun Kwak
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea.
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23
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Okada K, Uemura K, Kondo N, Sumiyoshi T, Seo S, Otsuka H, Serikawa M, Ishii Y, Tsuboi T, Murakami Y, Takahashi S. Neoadjuvant therapy contributes to nodal downstaging of pancreatic cancer. Langenbecks Arch Surg 2021; 407:623-632. [PMID: 34609618 DOI: 10.1007/s00423-021-02339-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 09/21/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE This study aimed to assess the impact of neoadjuvant therapy (NAT) for borderline resectable or locally advanced pancreatic cancer (BR/LAPC) on the American Joint Commission on Cancer (AJCC) nodal status. METHODS The medical records of BR/LAPC patients who underwent surgery with curative intent were retrospectively reviewed. The nodal status was compared between patients who underwent upfront surgery (UFS) and those who received NAT. Moreover, clinicopathological factors and prognostic factors for overall survival were analyzed. RESULTS In all, 200 patients with BR/LAPC, 78 with UFS, and 122 with NAT were enrolled. The nodal status was significantly lower in patients after NAT than after UFS (p = 0.011). A multivariate analysis of overall survival showed that UFS (hazard ratio (HR) 1.61, p = 0.024) and N2 status (HR 2.69, p < 0.001) were independent poor prognostic factors. The median serum carbohydrate antigen (CA) 19-9 level after NAT in N2 patients was 105 U/mL, which was significantly higher than that of patients with N0 (p = 0.004) and N1 (p = 0.008) status. CONCLUSION Patients with BR/LAPC who underwent surgery after NAT had significantly lower N2 status and better prognosis than patients who underwent UFS. Elevated CA19-9 levels after NAT indicated a higher nodal status.
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Affiliation(s)
- Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Naru Kondo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shingo Seo
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroyuki Otsuka
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomofumi Tsuboi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan
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24
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Zhu X, Chen D, Cao Y, Zhao X, Ju X, Shen Y, Cao F, Qing S, Fang F, Jia Z, Zhang H. Validation of the eighth edition of the AJCC staging system for patients with pancreatic adenocarcinoma initially receiving chemoradiotherapy and proposal of modifications. Cancer Biol Med 2021; 17:492-500. [PMID: 32587784 PMCID: PMC7309473 DOI: 10.20892/j.issn.2095-3941.2019.0101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 04/18/2019] [Indexed: 12/31/2022] Open
Abstract
Objective: To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy, and to propose modifications to improve prognostic accuracy. Methods: Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system. Meanwhile, another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi (PV ± PVTT) were retrieved for survival comparisons. Modifications were proposed according to the survival comparisons. A cohort from the SEER database was used for external validation of the modified staging system. Results: A total of 683 patients were included. Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition. The survival of patients with PV ± PVTT was comparable to that of patients with T4 tumors. The concordance index of the seventh and eighth editions, and the modified staging system was 0.744 (95%CI: 0.718–0.769), 0.750 (95%CI: 0.725–0.775), and 0.788 (95%CI: 0.762–0.813), respectively. For external validation, the concordance index was 0.744 (95%CI: 0.718–0.770), 0.750 (95%CI: 0.724–0.776), and 0.788 (95%CI: 0.762–0.814), respectively. Conclusions: The modified staging system is suggested to have the most accurate prognostic value. Hence, PV ± PVTT should be added to the definition of T4 tumors regardless of tumor size. Patients with N2 or N1 in different T stages could be regrouped into different substages. Additionally, stage III should be subclassified into IIIA (T3N2 and T4N0) and IIIB (T4N1-2).
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Affiliation(s)
- Xiaofei Zhu
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Di Chen
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Yangsen Cao
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Xianzhi Zhao
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Xiaoping Ju
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Yuxin Shen
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Fei Cao
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Shuiwang Qing
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Fang Fang
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Zhen Jia
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
| | - Huojun Zhang
- Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai 200433, China
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Chen C, Rui Z, Yuhan W, Yongjie Z, Yinghe Q, Ning Y, Tianqiang S, Jianying L, Jiangtao L, Xianhai M, Shengping L, Shubin S, Zhiqiang C, Zhaohui T, Zhimin G. Optimal Lymph Node Staging System in Evaluating Prognosis of Gallbladder Carcinoma: A Multi-institutional Study. Ann Surg Oncol 2021; 28:8142-8151. [PMID: 34532819 DOI: 10.1245/s10434-021-10749-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 07/24/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Lymph node (LN) involvement is a critical prognostic factor in patients with gallbladder carcinoma (GBC). Controversy exists regarding optimal categorization of nodal metastasis status, including anatomical location of positive nodes (AJCC 7th N staging), number of metastatic lymph nodes (NMLN), log odds of metastatic LNs (LODDS), and lymph node ratio (LNR). METHODS Patients who underwent curative-intent resection for GBC from six Chinese tertiary hospitals between 2008 and 2013 were analyzed retrospectively. The relative discriminative abilities of the different LN staging systems were assessed by different models including the tree-augmented naïve Bayesian (TAN) model, Cox proportional hazards regression model, and binary logistic regression model. RESULTS A total of 226 patients were involved in this cohort. Based on the TAN model and composite importance measures, the most important factor affecting the prognosis in the different LN staging systems was NMLN. Among the four TAN models which were built with 4 metastatic LN markers and baseline variables, the accuracy of the NMLN-based prognostic model was 88.15%, higher than 7th N staging (86.44%), LNR (87.34%), and LODDS (85.19%). The Cox model based on NMLN (C-index: 0.763, AIC: 1371.62) had a higher fitness than the others (7th N staging C-index: 0.756, AIC: 1375.51; LNR C-index: 0.759, AIC: 1378.82; LODDS C-index 0.748, AIC: 1390.99). The AUCs of different staging binary logistic regression models were NMLN (0.872), LNR (0.872), 7th N staging (0.869) and LODDS (0.856), respectively. CONCLUSIONS NMLN was the optimal LN staging system in evaluating prognosis of GBC.
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Affiliation(s)
- Chen Chen
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhang Rui
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wu Yuhan
- Department of Industrial Engineering, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an, China
| | - Zhang Yongjie
- Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Affiliated to Naval Medical University, Shanghai, China
| | - Qiu Yinghe
- Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Affiliated to Naval Medical University, Shanghai, China
| | - Yang Ning
- Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Affiliated to Naval Medical University, Shanghai, China
| | - Song Tianqiang
- Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Hospital, Tianjin, China
| | - Lou Jianying
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Li Jiangtao
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Mao Xianhai
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, China
| | - Li Shengping
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Si Shubin
- Department of Industrial Engineering, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an, China
| | - Cai Zhiqiang
- Department of Industrial Engineering, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an, China
| | - Tang Zhaohui
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
| | - Geng Zhimin
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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26
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Hu H, Qu C, Tang B, Liu W, Ma Y, Chen Y, Xie X, Zhuang Y, Gao H, Tian X, Yang Y. Validation and modification of the AJCC 8th TNM staging system for pancreatic ductal adenocarcinoma in a Chinese cohort: A nationwide pancreas data center analysis. Chin J Cancer Res 2021; 33:457-469. [PMID: 34584371 PMCID: PMC8435826 DOI: 10.21147/j.issn.1000-9604.2021.04.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 07/18/2021] [Indexed: 12/11/2022] Open
Abstract
Objective To validate the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC. Methods Data were collected from the China Pancreas Data Center (CPDC) for patients with resected PDAC in 2016 and 2017, and cancer-specific survival (CSS) was evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors. The recursive partitioning analysis (RPA), Kaplan-Meier method, and log-rank test were performed on the training dataset to generate a proposed modification for the 8th TNM staging system utilizing the preoperative carbohydrate antigen (CA)19-9 level. Validation was performed for both staging systems in the validation cohort. Results A total of 1,676 PDAC patients were retrieved, and the median CSS was significantly different between the 8th TNM groupings, with no significant difference in survival between stage IB and IIA. The analysis of T and N stages demonstrated a better prognostic value in the N category. Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors. All patients with CA19-9 >500 U/mL had similar survival, and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III. The modified staging system had a better performance for predicting CSS than the 8th AJCC staging scheme. Conclusions The 8th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients, and the N category has a better prognostic value than the T category. Our modified staging system has superior accuracy in predicting survival than the 8th AJCC TNM staging system.
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Affiliation(s)
- Hao Hu
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China.,Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing 100049, China
| | - Chang Qu
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Bingjun Tang
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Weikang Liu
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Yongsu Ma
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Yiran Chen
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Xuehai Xie
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Yan Zhuang
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Hongqiao Gao
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Xiaodong Tian
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
| | - Yinmo Yang
- Department of General Surgery, Peking University First Hospital, Beijing 100034, China
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Miyata Y, Yonamine N, Fujinuma I, Tsunenari T, Takihata Y, Iwasaki T, Einama T, Tsujimoto H, Ueno H, Yamamoto J, Kishi Y. Impact of Lymph Node Metastases Around the Superior Mesenteric Artery on Postoperative Outcomes of Pancreatic Head Cancer. World J Surg 2021; 45:3668-3676. [PMID: 34406453 DOI: 10.1007/s00268-021-06276-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND The neural plexus and lymph nodes around the superior mesenteric artery (LN#14), are the most frequent sites involved by pancreatic head cancer. However the influence of metastases to LN#14 on patients' prognosis has rarely been evaluated. METHODS The patients who underwent pancreatectomy for pancreatic head cancer between January 2010 and December 2018 were selected. The patients with nodal metastases were classified into an LN#14 + or LN#14-group according to LN#14 metastasis. Clinical and pathological characteristics and prognosis were compared between the two groups. RESULTS In total, 99 patients underwent pancreatectomy. Ninety-four patients were positive for lymph node metastases and 14 and 80 were classified as LN#14 + and LN#14 - , respectively. Postoperative median overall survival (OS) of the LN#14 + and LN#14 - groups was 10.2 and 31.1 months, respectively (P < 0.001). Median OS of the LN#14 + group was worse than that of patients with ≥ 4 metastatic nodes in the LN#14 - group (n = 35, 24.7 months, P = 0.002). In multivariate analysis, LN#14 + (hazard ratio [HR] = 3.89, 95% confidence interval [CI], 1.64-8.86) was one of the independent predictors of worse OS. CONCLUSION It might be feasible to recognize LN#14 metastases as an important prognostic factor independently from other regional lymph node metastases.
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Affiliation(s)
- Yoichi Miyata
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Naoto Yonamine
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Ibuki Fujinuma
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takazumi Tsunenari
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Yasuhiro Takihata
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Toshimitsu Iwasaki
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takahiro Einama
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hironori Tsujimoto
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Junji Yamamoto
- Department of Gastrointestinal Surgery, Ibaraki Prefectural Central Hospital, Ibaraki, 309-1793, Japan
| | - Yoji Kishi
- Department of Surgery, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
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Kong HH, Kim KW, Ko YS, Kim SC, Lee JH, Song KB, Hwang DW, Kim W. Longitudinal Changes in Body Composition of Long-Term Survivors of Pancreatic Head Cancer and Factors Affecting the Changes. J Clin Med 2021; 10:3436. [PMID: 34362219 PMCID: PMC8348760 DOI: 10.3390/jcm10153436] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 07/26/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Previous studies on changes in body composition of pancreatic cancer patients have only focused on short-term survivors. We studied longitudinal body composition changes and factors affecting them in long-term survivors by analyzing many abdominal computed tomography images using artificial intelligence technology. Of 302 patients who survived for >36 months after surgery were analyzed. Multivariate logistic regression analysis for factors affecting body composition changes and repeated-measures analysis of variance to observe differences in the course of change according to each factor were performed. In logistic analysis, preoperative sarcopenia and recurrence were the main factors influencing body composition changes at 1 and 3 years after surgery, respectively. In changes of longitudinal body composition, the decrease in body composition was the greatest at 3-6 months postoperatively, and the preoperative status did not recover even 3 years after surgery. Especially, males showed a greater reduction in skeletal muscle (SKM) after surgery than females (p < 0.01). In addition, SKM (p < 0.001) and subcutaneous adipose tissue (p < 0.05) mass rapidly decreased in case of recurrence. In conclusion, long-term survivors of pancreatic cancer did not recover their preoperative body composition status, and preoperative sarcopenia and recurrence influenced body composition changes.
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Affiliation(s)
- Hyun-Ho Kong
- Department of Rehabilitation Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea;
| | - Kyung-Won Kim
- Department of Radiology, Asan Image Metrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (K.-W.K.); (Y.-S.K.)
| | - You-Sun Ko
- Department of Radiology, Asan Image Metrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (K.-W.K.); (Y.-S.K.)
| | - Song-Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.-C.K.); (J.-H.L.); (K.-B.S.)
| | - Jae-Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.-C.K.); (J.-H.L.); (K.-B.S.)
| | - Ki-Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.-C.K.); (J.-H.L.); (K.-B.S.)
| | - Dae-Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.-C.K.); (J.-H.L.); (K.-B.S.)
| | - Won Kim
- Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
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The role of radiotherapy for pancreatic malignancies: a population-based analysis of the SEER database. Clin Transl Oncol 2021; 24:76-83. [PMID: 34219204 PMCID: PMC8732853 DOI: 10.1007/s12094-021-02671-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/14/2021] [Indexed: 12/24/2022]
Abstract
Background To investigate the role of adjuvant radiotherapy in patients with pancreatic cancer. Methods and patients The patients with pancreatic cancer from 18 registered institutions in the Surveillance Epidemiology and End Results (SEER) database were retrospectively analyzed. The characteristics of patients who would benefit from adjuvant radiotherapy were screened, as well as whether neoadjuvant or adjuvant radiotherapy conferred to a better clinical outcome. Propensity score matching was used to control for confounding features. Results Thirty thousand two hundred and forty-nine patients were included in this study (21,295 vs 8954 in surgery and adjuvant radiotherapy group); 1150 patients were matched in two groups. The median survivals in the surgery (S) group and adjuvant radiotherapy (S + R) group were 24 and 21 months, respectively. The 1-, 3-, and 5-year overall survival (OS) rates in the S group and S + R group were 68%, 40%, 31%, and 75%, 30%, 20%, respectively (p < 0.001), and the median OS was 22 and 25 months in S and S + R group after PSM, the former 1-, 2-, 3-, and 5-year OS were 73%, 45%, 30%, and 19%, and the later were 81%, 52%, 37%, and 24% (p = 0.0015), respectively; stratified analysis showed patients whose carcinoma located at pancreatic head with II stage infiltrating duct carcinoma (22 vs 25, p = 0.0276), T4 adenocarcinoma (28 vs 33, p = 0.0022), N1 stage adenocarcinoma (20 vs 23, p = 0.0203), and patients with infiltrating duct carcinoma received regional resection (23 vs 25, p = 0.028) and number of resected lymph node were ≥ 4 (22 vs 25, p = 0.009) had better OS after additional radiotherapy than surgery alone. Patients with pancreatic body/tail carcinoma III stage adenocarcinoma (13 vs, p = 0.0503) and T4 adenocarcinoma (14 vs, p = 0.0869) had survival advantage within 24 months for additional radiotherapy. However, patients with T2 stage adenocarcinoma located in pancreatic body/tail had better OS in surgery group than that in R + S group. Conclusions Additional radiotherapy may contribute to improved prognosis for patients with pancreatic head II stage infiltrating duct carcinoma, III stage adenocarcinoma, T4 stage carcinoma, N1 stage adenocarcinoma, regional resection, or number of lymphadenectomy ≥ 4 in infiltrating duct carcinoma. A specific subgroup of patients with specific stage and histological type pancreatic cancer should be considered for additional radiotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s12094-021-02671-0.
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Chin KM, Di Martino M, Syn N, Ielpo B, Hilal MA, Goh BKP, Koh YX, Prieto M. Re-appraising the role of lymph node status in predicting survival in resected distal cholangiocarcinoma - A meta-analysis and systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:1267-1277. [PMID: 33549378 DOI: 10.1016/j.ejso.2021.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/22/2020] [Accepted: 01/06/2021] [Indexed: 02/08/2023]
Abstract
This systematic review and meta-analysis aimed to confirm the prognostic value of lymph node ratio (LNR), and determine an optimal LNR cut-off for overall survival (OS) in patients with distal cholangiocarcinoma (DCC) undergoing curative surgery. We additionally aimed to provide a consolidated review of current evidence regarding prognostic significance of positive lymph node count (PLNC) and total lymph node count (TLNC). A systematic search of PubMed, EMBASE and Cochrane Library was conducted from inception to October 2020. Studies were included into meta-analysis if there was histological diagnosis, curative surgery, restriction to DCC and relevant LNR results. Quality assessment was performed using the Newcastle Ottawa Scale. Findings for 1228 patients were pooled across 6 studies. Meta-analysis delineated a dose-effect gradient in which higher LNR cut-offs correlated with larger pooled hazard ratios: 0<LNR<0.2 (HR 1.54; 95% CI 1.08-2.20; p = 0.02), LNR>0.2 (HR 3.26; 95% CI 2.07-5.13; p < 0.00001) and LNR>0.4 (HR 3.59; 95% CI 2.31-5.58; p < 0.00001) when compared against a control group of LNR = 0. LNR of 0.2 (HR 2.12; 95% CI: 1.57-2.86; p < 0.0001) was found to be a significant and ideal cut-off for prognostication of poorer OS. A review of current literature reveals an ongoing debate regarding the comparative prognostic value of differing PLNC cut-offs (0/1/3 versus 0/1/4). TLNC of 10-13 is widely reported to be the minimum necessary to ensure improved long term outcomes. PLNC and LNR are strong prognostic factors for OS in DCC. An ideal LNR cut-off of 0.2 is most significantly associated with poorer OS.
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Affiliation(s)
- Ken Min Chin
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore
| | - Marcello Di Martino
- Hepatopancreatobiliary Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Calle de Diego de León, 62, 28006 Madrid, Spain
| | - Nicholas Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore
| | - Benedetto Ielpo
- Hepatopancreatobiliary Unit, Parc Salut Mar Hospital, Barcelona, Passeig Marítim de La Barceloneta 25, 08003, Spain
| | - Mohammad Abu Hilal
- Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Via Leonida Bissolati, 57, 25124, Italy
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore 10 Medical Drive, 117597, Singapore; Duke NUS Medical School, Singapore (8 College Rd, 169857, Singapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital 20 College Road, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore 10 Medical Drive, 117597, Singapore; Duke NUS Medical School, Singapore (8 College Rd, 169857, Singapore.
| | - Mikel Prieto
- Hepatobiliary Surgery and Liver Transplant Unit, Cruces University Hospital, Cruces Plaza, S/N, 48903 Barakaldo, Bizkaia, Spain; BioCruces Research Institute, University of the Basque Country Cruces Plaza, 48903 Barakaldo, Bizkaia, Spain
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Wu C, Hou SZ, Wu Z, Huang X, Wang Z, Tian B. Prognostic Nomogram for patients undergoing radical Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. BMC Cancer 2021; 21:624. [PMID: 34044806 PMCID: PMC8161963 DOI: 10.1186/s12885-021-08295-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 05/05/2021] [Indexed: 02/08/2023] Open
Abstract
Background Radical pancreaticoduodenectomy is the most common treatment strategy for patients diagnosed with adenocarcinoma of the pancreatic head. Few studies have reported the clinical characteristics and treatment efficacies of patients undergoing radical pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. Methods A total of 177 pancreatic head cancer patients who underwent radical pancreaticoduodenectomy and were pathologically confirmed as having pancreatic ductal adenocarcinoma were screened in the West China Hospital of Sichuan University. The multivariate analysis results were implemented to construct a nomogram. The concordance index (c-index), the area under the curve (AUC) and calibration were utilized to evaluate the predictive performance of the nomogram. Results The prognostic nutritional index (PNI), the lymph node ratio (LNR) and the American Joint Committee on Cancer (AJCC) staging served as independent prognostic factors and were used to construct the nomogram. The c-indexes of the nomogram were 0.799 (confidence interval (CI), 0.741–0.858) and 0.732 (0.657–0.807) in the primary set and validation set, respectively. The AUCs of the nomogram at 1 and 3 years were 0.832 and 0.783, which were superior to the AJCC staging values of 0.759 and 0.705, respectively. Conclusions The nomogram may be used to predict the prognosis of radical resection for adenocarcinoma of the pancreatic head. These findings may represent an effective model for the developing an optimal therapeutic schedule for malnourished patients who need early effective nutritional intervention and may promote the treatment efficacy of resectable adenocarcinoma of the pancreatic head. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08295-5.
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Affiliation(s)
- Chao Wu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Sheng Zhong Hou
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Zuowei Wu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Xing Huang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Zihe Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Bole Tian
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China.
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Rittmann MC, Hussung S, Braun LM, Klar RFU, Biesel EA, Fichtner-Feigl S, Fritsch R, Wittel UA, Ruess DA. Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma. Sci Rep 2021; 11:7499. [PMID: 33820913 PMCID: PMC8021576 DOI: 10.1038/s41598-021-86779-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 03/19/2021] [Indexed: 01/01/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC. Peripheral blood samples from 14 PDAC patients divided into three groups according to their time to tumor recurrence after curatively intended resection (early: < 6 months, medium: 6–12 months, late: > 12 months) underwent targeted proteome analysis. Proteins most strongly discriminating early and late recurrence were then examined in a number of established PDAC cell lines and their culture supernatants. Finally, PDAC organoid lines from primary tumors of patients with early and late recurrence were analyzed for confirmation and validation of results. In total, 23 proteins showed differential abundance in perioperative plasma from PDAC patients with early recurrence when compared to patients with late recurrence. Following confirmation of expression on a transcriptional and translational level in PDAC cell lines we further focused on three upregulated (MAEA, NT5E, AZU1) and two downregulated proteins (ATP6AP2, MICA). Increased expression of NT5E was confirmed in a subset of PDAC organoid cultures from tumors with early recurrence. MICA expression was heterogeneous and ATP6AP2 levels were very similar in both organoids from early and late recurrent tumors. Most strikingly, we observed high MAEA expression in all tested PDAC (n = 7) compared to a non-cancer ductal organoid line. MAEA also demonstrated potential to discriminate early recurrence from late recurrence PDAC organoids. Our study suggests that identification of plasma protein biomarkers released by tumor cells may be feasible and of value to predict the clinical course of patients. Prediction of recurrence dynamics would help to stratify up-front resectable PDAC patients for neoadjuvant chemotherapy approaches in an individualized fashion. Here, MAEA and NT5E were the most promising candidates for further evaluation.
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Affiliation(s)
- Marie-Claire Rittmann
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Saskia Hussung
- Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Department of Medical Oncology and Hematology, Zurich University Hospital, Zurich, Switzerland
| | - Lukas M Braun
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.,Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Rhena F U Klar
- Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Esther A Biesel
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Ralph Fritsch
- Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Department of Medical Oncology and Hematology, Zurich University Hospital, Zurich, Switzerland
| | - Uwe A Wittel
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
| | - Dietrich A Ruess
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
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Preoperative risk factors for para-aortic lymph node positivity in pancreatic cancer. Pancreatology 2021; 21:606-612. [PMID: 33648880 DOI: 10.1016/j.pan.2021.01.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE This study aimed to identify the preoperative risk factors for para-aortic lymph node (PALN) positivity, including micrometastasis, in pancreatic cancer. METHODS Medical records of patients with pancreatic cancer who underwent curative resection were retrospectively reviewed, and the relationships between preoperative risk factors and PALN positivity were identified. Clinicopathological and prognostic factors for overall survival were analyzed. Micrometastasis was investigated by immunohistochemistry. RESULTS 400 patients were enrolled. PALN positivity by hematoxylin and eosin staining, micrometastasis, and negative were found in 46 (11%), 32 (8%), and 322 (81%) patients, respectively. The median overall survival times of patients with PALN positivity, including micrometastasis, was 22.5 months. Multivariate logistic regression identified borderline or locally advanced status (p=0.037), elevated preoperative carbohydrate antigen (CA) 19-9 level (p<0.001), larger tumor size ≥30 mm (p=0.001) and larger PALN size ≥10 mm (p=0.019) as independent preoperative risk factors of PALN positivity. Multivariate overall survival analysis demonstrated borderline or locally advanced status (p=0.013), elevated preoperative CA19-9 level (p<0.001) and PALN positivity (p=0.048) were independent poor prognostic factors. CONCLUSIONS Borderline or locally advanced status, elevated preoperative CA19-9 level, and larger tumor and PALN size were risk factors for PALN positivity, and thus, they may contribute to the optimization of preoperative treatments for patients with potential PALN positivity.
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Weyhe D, Obonyo D, Uslar VN, Stricker I, Tannapfel A. Predictive factors for long-term survival after surgery for pancreatic ductal adenocarcinoma: Making a case for standardized reporting of the resection margin using certified cancer center data. PLoS One 2021; 16:e0248633. [PMID: 33735191 PMCID: PMC7971889 DOI: 10.1371/journal.pone.0248633] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 03/02/2021] [Indexed: 12/15/2022] Open
Abstract
Factors for overall survival after pancreatic ductal adenocarcinoma (PDAC) seem to be nodal status, chemotherapy administration, UICC staging, and resection margin. However, there is no consensus on the definition for tumor free resection margin. Therefore, univariate OS as well as multivariate long-term survival using cancer center data was analyzed with regards to two different resection margin definitions. Ninety-five patients met inclusion criteria (pancreatic head PDAC, R0/R1, no 30 days mortality). OS was analyzed in univariate analysis with respect to R-status, CRM (circumferential resection margin; positive: ≤1mm; negative: >1mm), nodal status, and chemotherapy administration. Long-term survival >36 months was modelled using multivariate logistic regression instead of Cox regression because the distribution function of the dependent data violated the requirements for the application of this test. Significant differences in OS were found regarding the R status (Median OS and 95%CI for R0: 29.8 months, 22.3–37.4; R1: 15.9 months, 9.2–22.7; p = 0.005), nodal status (pN0 = 34.7, 10.4–59.0; pN1 = 17.1, 11.5–22.8; p = 0.003), and chemotherapy (with CTx: 26.7, 20.4–33.0; without CTx: 9.7, 5.2–14.1; p < .001). OS according to CRM status differed on a clinically relevant level by about 12 months (CRM positive: 17.2 months, 11.5–23.0; CRM negative: 29.8 months, 18.6–41.1; p = 0.126). A multivariate model containing chemotherapy, nodal status, and CRM explained long-term survival (p = 0.008; correct prediction >70%). Chemotherapy, nodal status and resection margin according to UICC R status are univariate factors for OS after PDAC. In contrast, long-term survival seems to depend on wider resection margins than those used in UICC R classification. Therefore, standardized histopathological reporting (including resection margin size) should be agreed upon.
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Affiliation(s)
- Dirk Weyhe
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Dennis Obonyo
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Verena Nicole Uslar
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
- * E-mail:
| | - Ingo Stricker
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
| | - Andrea Tannapfel
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
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Li P, Song L. A novel prognostic nomogram for patients with surgically resected perihilar cholangiocarcinoma: a SEER-based study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:54. [PMID: 33553347 PMCID: PMC7859751 DOI: 10.21037/atm-20-3130] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background This study aimed to compare the predictive efficacy of four different lymph node (LN) staging systems on the overall survival (OS) of patients with surgically resected perihilar cholangiocarcinoma (pCCA), and construct a novel prognostic nomogram to predict OS in pCCA patients. Methods Patients with pCCA that underwent surgical resection between 2004 to 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database (n=1,173). Patients were randomly divided into a modeling cohort and an internal verification cohort. To compare the prognostic efficacy of four different N staging systems [American Joint Committee on Cancer (AJCC) 7th and 8th edition N stages, lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS)], we used three different evaluation methods: Harrell's index of concordance (C-index), Akaike information criterion (AIC), and area under the receiver operating characteristic (ROC) curve (AUC). Multivariate analysis was used to identify independent prognostic factors and validate LODDS in the modeling cohort. A nomogram was then constructed to predict 1-, 3-, and 5-year survival. The nomogram was validated using Harrell's C-indexes and calibration curves. Results Of the four different N staging methods, LODDS was considered to be the most effective LN staging system for evaluating the prognosis of patients with surgically resected pCCA, according to the values calculated for C-index, AUC, and AIC. After validation by C-indexes and calibration curves, the constructed nomogram accurately predicted the OS of pCCA patients. Conclusions For patients with surgically resected pCCA, LODDS was found to be the most accurate N staging system. The novel LODDS-based nomogram constructed in this study provides an accurate method for predicting patient survival in pCCA.
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Affiliation(s)
- Pengfei Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lujun Song
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Saluja SS, Mishra PK, Kiran S, Shah HJ, Chandrasekar S, Nayeem M, Sharma A, Varshney VK. Impact of lymph node staging systems in predicting outcome in patients with ampullary cancer. Ann Hepatobiliary Pancreat Surg 2020; 24:484-495. [PMID: 33234752 PMCID: PMC7691202 DOI: 10.14701/ahbps.2020.24.4.484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 11/02/2022] Open
Abstract
Backgrounds/Aims Lymph node (LN) metastasis though, is a poor prognostic factor for ampullary carcinoma (APC), the impact of Lymph node ratio (LNR) and Logarithm odds of positive lymph node (LODDS) in the long-term survival remains controversial. We evaluated the factors affecting the long-term outcome in APC patients with emphasis on LNR and LODDS. Methods The prospectively collected data of 198 patients who underwent pancreatoduodenectomy for APC was analyzed after excluding 12 patients for various reasons. Factors affecting Disease specific survival (DSS) and Recurrence free survival (RFS) were analyzed with special reference to LN positivity, LNR and LODDS. Results Out of 186, 117 (62.9%) patients were alive at a median follow-up of 39.5 months and 72 (38.7%) developed recurrence. The overall 5-year DSS was 59.3% & RFS 54.9%. Univariate analysis showed T-stage, tumor differentiation, perineural invasion, LN positivity, LNR and LODDS was significantly affected DSS and RFS. On multivariate analysis, perineural invasion, LN positivity, LNR and LODDS lost its significance for DSS and RFS. AUC for prediction of DSS and RFS for LNR was 0.654 (p<0.001) & 0.629 (p=0.003) respectively and for LODDS, it was 0.697 (p<0.001) & 0.677 (p=0.001) respectively. Sensitivity and specificity of LNR (0.1) for DSS were 37.7% & 83.8% and for RFS were 36.1% & 83.3%; for LODDS (-1.00), sensitivity and specificity for DSS was 62.3% and 67.5% and for RFS it was 59.7% and 66.7% respectively. Conclusions LNR and LODDS although independently seem to affect the RFS and DSS, albeit have a low sensitivity and specificity in predicting DSS and RFS.
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Affiliation(s)
- Sundeep Singh Saluja
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Pramod Kumar Mishra
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Shashi Kiran
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Harsh J Shah
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Sandip Chandrasekar
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Mohammed Nayeem
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Aditya Sharma
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Vaibhav Kumar Varshney
- Department of Gastrointestinal Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
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Abstract
Importance In the past few decades, there has been rapid advancements in imaging technologies that have become irreplaceable in the pre-operative assessment of patients with pancreatic tumors. Modern imaging modalities, including computed tomography (CT) and endoscopic ultrasound (EUS), can provide critical information of the absence or presence of metastatic disease in pancreatic cancer, as well as details on the local extent and resectability, allowing for the selection of stage appropriate treatments and pre-operatively determined surgical approach. Objective The aim of this review is to discuss staging, resectability, and imaging for patients with pancreatic tumors. Evidence Review A literature review was performed of articles relevant to the topics of staging, resectability, and imaging of pancreatic tumors. Imaging modalities included CT, EUS, magnetic resonance imaging (MRI), positron emission tomography (PET), antibody-based and narrow band imaging. Findings CT pancreas protocol combined with EUS serve as the primary modalities in diagnosis, staging, and surgical planning in patients with pancreatic tumors. MRI is an alternative to CT with near equivalent utility in the pre-operative setting. In some circumstances, PET-CT may be a cost-effective initial study to detect distant disease. Conclusions and Relevance Current imaging technologies play a critical role in the evaluation of patients with pancreatic tumors. Advances in the past 3 decades in imaging technologies have revolutionized the process of assessment of stage and resectability in patients with pancreatic tumors. Future imaging technologies will address current limitation in the evaluation of occult metastatic disease.
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Li MX, Wang HY, Yuan CH, Ma CL, Jiang B, Li L, Zhang L, Zhao H, Cai JQ, Xiu DR. The eighth version of American Joint Committee on Cancer nodal classification for high grade pancreatic neuroendocrine tumor should be generalized for the whole population with this disease. Medicine (Baltimore) 2020; 99:e22089. [PMID: 32925749 PMCID: PMC7489597 DOI: 10.1097/md.0000000000022089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all).The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.
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Affiliation(s)
- Mu-xing Li
- Department of General Surgery, Peking University Third Hospital
| | - Hang-yan Wang
- Department of General Surgery, Peking University Third Hospital
| | - Chun-hui Yuan
- Department of General Surgery, Peking University Third Hospital
| | - Chao-lai Ma
- Department of General Surgery, Peking University Third Hospital
| | - Bin Jiang
- Department of General Surgery, Peking University Third Hospital
| | - Lei Li
- Department of General Surgery, Peking University Third Hospital
| | - Li Zhang
- Department of General Surgery, Peking University Third Hospital
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R.China
| | - Jian-qiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R.China
| | - Dian-rong Xiu
- Department of General Surgery, Peking University Third Hospital
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Role of lymphadenectomy in resectable pancreatic cancer. Langenbecks Arch Surg 2020; 405:889-902. [PMID: 32902706 DOI: 10.1007/s00423-020-01980-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 08/31/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Pancreatic cancer (PC) remains one of the most devastating malignant diseases, predicted to become the second leading cause of cancer-related death by 2030. Despite advances in surgical techniques and in systemic therapy, the 5-year relative survival remains a grim 9% for all stages combined. The extent of lymphadenectomy has been discussed intensively for decades, given that even in early stages of PC, lymph node (LN) metastasis can be detected in approximately 80%. PURPOSE The primary objective of this review was to provide an overview of the current literature evaluating the role of lymphadenectomy in resected PC. For this, we evaluated randomized controlled studies (RCTs) assessing the impact of extent of lymphadenectomy on OS and studies evaluating the prognostic impact of anatomical site of LN metastasis and the impact of the number of resected LNs on OS. CONCLUSIONS Lymphadenectomy plays an essential part in the multimodal treatment algorithm of PC and is an additional therapeutic tool to increase the chance for surgical radicality and to ensure correct staging for optimal oncological therapy. Based on the literature from the last decades, standard lymphadenectomy with resection of at least ≥ 15 LNs is associated with an acceptable postoperative complication risk and should be recommended to obtain local radicality and accurate staging of the disease. Although radical surgery including appropriate lymphadenectomy of regional LNs remains the only chance for long-term tumor control, future studies specifically assessing the impact of neoadjuvant therapy on extraregional LNs are warranted.
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Malleo G, Maggino L, Nobile S, Casciani F, Cacciatori N, Paiella S, Luchini C, Rusev B, Capelli P, Marchegiani G, Bassi C, Salvia R. Reappraisal of nodal staging and study of lymph node station involvement in distal pancreatectomy for body-tail pancreatic ductal adenocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1734-1741. [PMID: 32327367 DOI: 10.1016/j.ejso.2020.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/03/2020] [Accepted: 04/08/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND The pattern of nodal spread in body-tail pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study analyzed the characteristics of lymph node (LN) involvement and the prognostic role of nodal metastases stratified by LN stations. METHODS All upfront distal pancreatectomies (DPs) for PDAC (2000-2017) with complete information on station 8,10,11, and 18 were included. Clinico-pathological correlates and survival were investigated using uni- and multivariable analyses. RESULTS Among 100 included patients, 28 were N0, 42 N1 and 30 N2. The median number of examined LN was 32 (IQR 26-44). Tumor size at preoperative imaging increased across N-classes. Preoperative size >27.5 mm was associated with N2 status. The frequency of nodal metastases at stations 8, 9, 10, 11, and 18 was 12.0%, 10.9%, 3.0%, 71.0%, and 19%, respectively. The pattern of LN spread was independent from primary tumor location (with tail tumors metastasizing to station 8/9 and body tumors to station 10), while it was highly associated with N-class. At multivariable analysis, tumor grading, adjuvant treatment, station 9 and 10 metastases were independent prognostic factors in node-positive patients. CONCLUSIONS In patients undergoing upfront DP for PDAC preoperative tumor size is associated with the degree of nodal spread. While station 11 was the most frequently involved, only station-9 and 10 metastases were independent prognostic factors. The site of nodal metastases was somewhat unpredictable based on tumor location. This data has potential implications for allocating patients to neoadjuvant treatment and supports the performance of routine splenectomy during DP for PDAC.
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Affiliation(s)
- Giuseppe Malleo
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy.
| | - Laura Maggino
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Sara Nobile
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Fabio Casciani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Nicolò Cacciatori
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Luchini
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Borislav Rusev
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Paola Capelli
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Giovanni Marchegiani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
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Gao J, Han F, Jin Y, Wang X, Zhang J. A Radiomics Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma. Front Oncol 2020; 10:1654. [PMID: 32974205 PMCID: PMC7482654 DOI: 10.3389/fonc.2020.01654] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 07/28/2020] [Indexed: 12/17/2022] Open
Abstract
PURPOSE To construct and verify a CT-based multidimensional nomogram for the evaluation of lymph node (LN) status in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS We retrospectively assessed data from 172 patients with clinicopathologically confirmed PDAC surgically resected between February 2014 and November 2016. Patients were assigned to either a training cohort (n = 121) or a validation cohort (n = 51). We acquired radiomics features from the preoperative venous phase (VP) CT images. The maximum relevance-minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) methods were used to select the optimal features. We used multivariable logistic regression to construct a combined radiomics model for visualization in the form of a nomogram. Performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve approach, calibration testing, and analysis of clinical usefulness. RESULTS A Rad score consisting of 10 LN status-related radiomics features was found to be significantly associated with the actual LN status (P < 0.01). A nomogram that consisted of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status performed well in terms of predictive power in the training cohort (area under the curve, 0.92), and this was confirmed in the validation cohort (area under the curve, 0.95). The nomogram also performed well in the calibration test and decision curve analysis, demonstrating its potential clinical value. CONCLUSION A multidimensional radiomics nomogram consisting of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status may contribute to the non-invasive evaluation of LN status in PDAC patients.
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Affiliation(s)
| | | | | | | | - Jiawen Zhang
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
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Karjol U, Chandranath A, Jonnada P, Cherukuru S, Annavarjula V, Morla SA. Lymph Node Ratio as a Prognostic Marker in Pancreatic Cancer Survival: A Systematic Review and Meta-Analysis. Cureus 2020; 12:e9597. [PMID: 32789099 PMCID: PMC7417066 DOI: 10.7759/cureus.9597] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Introduction The lymph node ratio (LNR) is defined as the ratio of number of positive lymph nodes to the total number of lymph nodes harvested during surgery. The objective of this article is to investigate the efficacy of LNR as a prognostic indicator of survival in pancreatic cancer patients who have undergone surgery by meta-analysis. Methods A systematic database search was performed in MEDLINE, Embase, and Google Scholar for relevant studies that reported LNR in pancreatic cancer. Two authors independently screened the relevant articles for selection and to extract data. All studies published in English up to April 2020 were obtained, and a total of 17,128 node-positive patients in 14 studies were included in this meta-analysis. RevMan software 5.3 (Cochrane Collaboration, the Nordic Cochrane Centre, Copenhagen, Denmark) was used for conducting all statistical analyses. Results This meta-analysis demonstrated that LNR > 0.2 significantly correlated with worse survival (hazard ratio [HR]: 1.84; 95% CI: 1.74-1.94; p ≤ 0.00001) in node-positive pancreatic cancer patients. Conclusions Our findings have demonstrated that a higher LNR is a predictor of poor survival and that LNR serves as an independent prognostic marker for assessing survival using a cut-off of 20%.
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Affiliation(s)
- Uday Karjol
- Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, IND
| | - Ajay Chandranath
- Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, IND
| | - Pavan Jonnada
- Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, IND
| | | | - Vinitha Annavarjula
- Oral and Maxillofacial Surgery, Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, IND
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Shin J, Shin S, Lee JH, Song KB, Hwang DW, Kim HJ, Byun JH, Cho H, Kim SC, Hong SM. Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas. J Pathol Transl Med 2020; 54:387-395. [PMID: 32683855 PMCID: PMC7483027 DOI: 10.4132/jptm.2020.06.23] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 06/22/2020] [Indexed: 01/29/2023] Open
Abstract
Background Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis. Methods We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points. Results A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9±5.0 mm; short axis, 4.3±3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0±4.0 mm; short axis, 3.0±2.0 mm; all p<.001). Using a 10 mm cutoff, the sensitivity, specificity, positive predictive value, overall accuracy, and area under curve was 24.8%, 88.0%, 17.1%, 82.3%, and 0.60 for the long axis and 7.0%, 99.0%, 40.3%, 90.6%, and 0.61 for the short axis, respectively. Conclusions The metastatic nodes are larger than the non-metastatic nodes in PDAC patients. However, the difference in nodal size was too small to be identified with preoperative imaging. The performance of preoperative radiologic imaging to predict lymph nodal metastasis was not good. Therefore, nodal size cannot be used a surrogate preoperative marker of lymph node metastasis.
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Affiliation(s)
- Jaehoon Shin
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seungbeom Shin
- Department of Statistics, Korea University, Seoul, Korea
| | - Jae Hoon Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki Byung Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dae Wook Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - HyungJun Cho
- Department of Statistics, Korea University, Seoul, Korea
| | - Song Cheol Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Mundry CS, Eberle KC, Singh PK, Hollingsworth MA, Mehla K. Local and systemic immunosuppression in pancreatic cancer: Targeting the stalwarts in tumor's arsenal. Biochim Biophys Acta Rev Cancer 2020; 1874:188387. [PMID: 32579889 DOI: 10.1016/j.bbcan.2020.188387] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/13/2020] [Accepted: 06/15/2020] [Indexed: 02/06/2023]
Abstract
Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3rd leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens. However, the success of these studies depends on detailed examination and understanding of tumor-immune cell interactions, not only in the primary tumor but also at distant systemic niches. Innate and adaptive arms of the immune system sculpt tumor immunogenicity, where they not only aid in providing an amenable environment for their survival but also act as a driver for tumor relapse at primary or distant organ sites. This review article highlights the key events associated with tumor-immune communication and associated immunosuppression at both local and systemic microenvironments in PDAC. Furthermore, we discuss the approaches and benefits of targeting both local and systemic immunosuppression for PDAC patients. The present articles integrate data from clinical and genetic mouse model studies to provide a widespread consensus on the role of local and systemic immunosuppression in undermining the anti-tumor immune responses against PDAC.
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MESH Headings
- Adaptive Immunity/drug effects
- Animals
- Antineoplastic Agents, Immunological/pharmacology
- Antineoplastic Agents, Immunological/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/pharmacology
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Bone Marrow/drug effects
- Bone Marrow/immunology
- Bone Marrow/pathology
- Cancer Vaccines/administration & dosage
- Carcinoma, Pancreatic Ductal/immunology
- Carcinoma, Pancreatic Ductal/mortality
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/therapy
- Chemotherapy, Adjuvant/methods
- Clinical Trials as Topic
- Combined Modality Therapy/methods
- Disease Models, Animal
- Disease-Free Survival
- Fluorouracil/pharmacology
- Fluorouracil/therapeutic use
- Humans
- Immunity, Innate/drug effects
- Immunotherapy/methods
- Irinotecan/pharmacology
- Irinotecan/therapeutic use
- Leucovorin/pharmacology
- Leucovorin/therapeutic use
- Lymph Node Excision
- Lymph Nodes/immunology
- Lymph Nodes/pathology
- Lymph Nodes/surgery
- Mice
- Mice, Transgenic
- Neoadjuvant Therapy/methods
- Oxaliplatin/pharmacology
- Oxaliplatin/therapeutic use
- Pancreas/immunology
- Pancreas/pathology
- Pancreas/surgery
- Pancreatectomy
- Pancreatic Neoplasms/immunology
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/therapy
- Spleen/immunology
- Spleen/pathology
- Spleen/surgery
- Splenectomy
- T-Lymphocytes/drug effects
- T-Lymphocytes/immunology
- T-Lymphocytes/transplantation
- Transplantation, Autologous/methods
- Tumor Escape/drug effects
- Tumor Microenvironment/drug effects
- Tumor Microenvironment/immunology
- United States/epidemiology
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Affiliation(s)
- Clara S Mundry
- The Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
| | - Kirsten C Eberle
- The Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
| | - Pankaj K Singh
- The Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
| | - Michael A Hollingsworth
- The Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
| | - Kamiya Mehla
- The Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
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Li G, Chen JZ, Chen S, Lin SZ, Pan W, Meng ZW, Cai XR, Chen YL. Development and validation of novel nomograms for predicting the survival of patients after surgical resection of pancreatic ductal adenocarcinoma. Cancer Med 2020; 9:3353-3370. [PMID: 32181599 PMCID: PMC7221449 DOI: 10.1002/cam4.2959] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 02/17/2020] [Accepted: 02/19/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Pancreatic ductal adenocarcinoma (PDAC) is associated with high mortality, even after surgical resection. The existing predictive models for survival have limitations. This study aimed to develop better nomograms for predicting overall survival (OS) and cancer‐specific survival (CSS) in PDAC patients after surgery. Methods A total of 6323 PDAC patients were retrospectively recruited from the Surveillance, Epidemiology, and End Results (SEER) database and randomly allocated into training, validation, and test cohorts. Multivariate Cox regression analysis was conducted to identify significant independent factors for OS and CSS, which were used for construction of nomograms. The performance was evaluated, validated, and compared with that of the 8th edition AJCC staging system. Results Ten independent factors were significantly correlated with OS and CSS. The 1‐, 3‐, and 5‐year OS rates were 40%, 20%, and 15%, and 1‐, 3‐, and 5‐year CSS rates were 45%, 24%, and 19%, respectively. The nomograms were calibrated well, with c‐indexes of 0.640 for OS and 0.643 for CSS, respectively. Notably, relative to the 8th edition AJCC staging system, the nomograms were able to stratify each AJCC stage into three prognostic subgroups for more robust risk stratification. Furthermore, the nomograms achieved significant clinical validity, exhibiting wide threshold probabilities and high net benefit. Performance assessment also showed high predictive accuracy and reliability. Conclusions The predictive ability and reliability of the established nomograms have been validated, and therefore, these nomograms hold potential as novel approaches to predicting survival and assessing survival risks for PDAC patients after surgery.
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Affiliation(s)
- Ge Li
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jiang-Zhi Chen
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Shi Chen
- Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Sheng-Zhe Lin
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Wei Pan
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ze-Wu Meng
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xin-Ran Cai
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yan-Ling Chen
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
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Kulkarni NM, Soloff EV, Tolat PP, Sangster GP, Fleming JB, Brook OR, Wang ZJ, Hecht EM, Zins M, Bhosale PR, Arif-Tiwari H, Mannelli L, Kambadakone AR, Tamm EP. White paper on pancreatic ductal adenocarcinoma from society of abdominal radiology's disease-focused panel for pancreatic ductal adenocarcinoma: Part I, AJCC staging system, NCCN guidelines, and borderline resectable disease. Abdom Radiol (NY) 2020; 45:716-728. [PMID: 31748823 DOI: 10.1007/s00261-019-02289-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal malignancy with a poor 5-year survival rate. Accurate staging of PDAC is an important initial step in the development of a stage-specific treatment plan. Different staging systems/consensus statements convened by different societies and academic practices are currently used. The most recent version of the American Joint Committee on Cancer (AJCC) tumor/node/metastases (TNM) staging system for PDAC has shifted its focus from guiding management to assessing prognosis. In order to preoperatively define the resectability of PDAC and to guide management, additional classification systems have been developed. The National Comprehensive Cancer Network (NCCN) guidelines, one of the most commonly used systems, provide recommendations on the management and the determination of resectability for PDAC. The NCCN divides PDAC into three categories of resectability based on tumor-vessel relationship: 'resectable,' 'borderline resectable,' and 'unresectable'. Among these, the borderline disease category is of special interest given its evolution over time and the resulting variations in the definition and the associated recommendations for management between different societies. It is important to be familiar with the evolving criteria, and treatment and follow-up recommendations for PDAC. In this article, the most current AJCC staging (8th edition), NCCN guidelines (version 2.2019-April 9, 2019), and challenges and controversies in borderline resectable PDAC are reviewed.
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Affiliation(s)
- Naveen M Kulkarni
- Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI, 53226, USA.
| | - Erik V Soloff
- Department of Radiology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA
| | - Parag P Tolat
- Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI, 53226, USA
| | - Guillermo P Sangster
- Department of Radiology, LSU Health - Shreveport Ochsner-LSU Health - Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA
| | - Jason B Fleming
- Gastrointestinal Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA
| | - Olga R Brook
- Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Shapiro 4, Boston, MA, 02215-5400, USA
| | - Zhen Jane Wang
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA
| | - Elizabeth M Hecht
- Department of Radiology, Columbia University Medical Center, 622 W 168th St, PH1-317, New York, NY, 10032, USA
| | - Marc Zins
- Department of Radiology, Groupe Hospitalier Paris Saint-Joseph, 185 Rue Raymond Losserand, 75014, Paris, France
| | - Priya R Bhosale
- Abdominal Imaging Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1473, Houston, TX, 77030-400, USA
| | - Hina Arif-Tiwari
- Department of Radiology, University of Arizona College of Medicine, 1501 N. Campbell Ave., P.O. Box 245067, Tucson, AZ, 85724, USA
| | | | - Avinash R Kambadakone
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, White 270, Boston, MA, 02114, USA
| | - Eric P Tamm
- Abdominal Imaging Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1473, Houston, TX, 77030-400, USA
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Warschkow R, Tsai C, Köhn N, Erdem S, Schmied B, Nussbaum DP, Gloor B, Müller SA, Blazer D, Worni M. Role of lymphadenectomy, adjuvant chemotherapy, and treatment at high-volume centers in patients with resected pancreatic cancer-a distinct view on lymph node yield. Langenbecks Arch Surg 2020; 405:43-54. [PMID: 32040705 DOI: 10.1007/s00423-020-01859-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 01/27/2020] [Indexed: 12/22/2022]
Abstract
PURPOSE While the importance of lymphadenectomy is well-established for patients with resectable pancreatic cancer, its direct impact on survival in relation to other predictive factors is still ill-defined. METHODS The National Cancer Data Base 2006-2015 was queried for patients with resected pancreatic adenocarcinoma (stage IA-IIB). Patients were dichotomized into the following two groups, those with 1-14 resected lymph nodes and those with ≥ 15. Optimal number of resected lymph nodes and the effect of lymphadenectomy on survival were assessed using various statistical modeling techniques. Mediation analysis was performed to differentiate the direct and indirect effect of lymph node resection on survival. RESULTS A total of 21,912 patients were included; median age was 66 years (IQR 59-73), 48.9% were female. Median number of resected lymph nodes was 15 (IQR 10-22), 10,163 (46.4%) had 1-14 and 11,749 (53.6%) had ≥ 15 lymph nodes retrieved. Lymph node positivity increased by 4.1% per lymph node up to eight examined lymph nodes, and by 0.6% per lymph node above eight. Five-year overall survival was 17.9%. Overall survival was better in the ≥ 15 lymph node group (adjusted HR 0.91, CI 0.88-0.95, p < 0.001). On a continuous scale, survival improved with increasing LNs collected. Patients who underwent adjuvant chemotherapy and were treated at high-volume centers had improved overall survival compared with their counterparts (adjusted HR 0.59, CI 0.57-0.62, p < 0.001; adjusted HR 0.86, CI 0.83-0.89, p < 0.001, respectively). Mediation analysis revealed that lymphadenectomy had only 18% direct effect on improved overall survival, while 82% of its effect were mediated by other factors like treatment at high-volume hospitals and adjuvant chemotherapy. DISCUSSION While higher number of resected lymph nodes increases lymph node positivity and is associated with better overall survival, most of the observed survival benefit is mediated by chemotherapy and treatment at high-volume centers.
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Affiliation(s)
- Rene Warschkow
- Department of Surgery, Kantonsspital St. Gallen, Gallen, Switzerland
| | - Catherine Tsai
- Department of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
| | - Nastassja Köhn
- Department of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
| | - Suna Erdem
- Department of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
| | - Bruno Schmied
- Department of Surgery, Kantonsspital St. Gallen, Gallen, Switzerland
| | - Daniel P Nussbaum
- Berner Viszeralchirurgie, Klinik Beau-Site, Hirslanden, Bern, Switzerland
| | - Beat Gloor
- Department of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
| | - Sascha A Müller
- Berner Viszeralchirurgie, Klinik Beau-Site, Hirslanden, Bern, Switzerland
| | - Dan Blazer
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Mathias Worni
- Department of Surgery, Duke University Medical Center, Durham, NC, USA. .,Swiss Institute for Translational and Entrepreneurial Medicine, Stiftung Lindenhof, Campus SLB, Bern, Switzerland. .,Clarunis, Department of Visceral Surgery, University Centre for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, CH-4058, Basel, Switzerland.
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Zheng ZJ, Wang MJ, Tan CL, Chen YH, Ping J, Liu XB. Prognostic impact of lymph node status in patients after total pancreatectomy for pancreatic ductal adenocarcinoma: A strobe-compliant study. Medicine (Baltimore) 2020; 99:e19327. [PMID: 32080152 PMCID: PMC7034702 DOI: 10.1097/md.0000000000019327] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 01/22/2020] [Accepted: 01/23/2020] [Indexed: 02/05/2023] Open
Abstract
The optimal number of examined lymph nodes (ELN) for staging and impact of nodal status on survival following total pancreatectomy (TP) for pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of this study was to evaluate the prognostic impact of different lymph node status after TP for PDAC.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients who underwent TP for PDAC from 2004 to 2015. We calculated overall survival (OS) of these patients using Kaplan-Meier analysis and Cox proportional hazards model.Overall, 1291 patients were included in the study, with 869 node-positive patients (49.5%). A cut-off points analysis revealed that 19, 19, and 13 lymph nodes best discriminated OS for all patients, node-negative patients, and node-positive patients, respectively. Higher number of ELN than the corresponding cut-off points was an independent predictor for better prognosis [all patients: hazard ratios (HR) 0.786, P = .002; node-negative patients: HR 0.714, P = .043; node-positive patients: HR 0.678, P < .001]. For node-positive patients, 1 to 3 positive lymph nodes (PLN) correlated independently with better survival compared with those with 4 or more PLN (HR 1.433, P = .002). Moreover, when analyzed in node-positive patients with less than 13 ELN, neither the number of PLN nor lymph node ratio (LNR) was associated with survival. However, when limited node-positive patients with at least 13 ELN, univariate analyses showed that both the number of PLN and LNR were associated with survival, whereas multivariate analyses demonstrated that only number of PLN was consistently associated with survival (HR 1.556, P = .004).Evaluation at least 19 lymph nodes should be considered as quality metric of surgery in patients who underwent TP for PDAC. For node-negative patients, a minimal number of 19 lymph nodes is adequate to avoid stage migration. For node-positive patients, PLN is superior to LNR in predicting survival after TP, predominantly for those with high number of ELN.
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Affiliation(s)
| | - Mo-Jin Wang
- Department of Gastrointestinal Surgery, Institute of Digestive Surgery and State key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | | | | | - Jie Ping
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, USA
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Liu P, Gu Q, Hu X, Tan X, Liu J, Xie A, Huang F. Applying a radiomics-based strategy to preoperatively predict lymph node metastasis in the resectable pancreatic ductal adenocarcinoma. JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY 2020; 28:1113-1121. [PMID: 33074215 DOI: 10.3233/xst-200730] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
PURPOSE This retrospective study is designed to develop a Radiomics-based strategy for preoperatively predicting lymph node (LN) status in the resectable pancreatic ductal adenocarcinoma (PDAC) patients. METHODS Eighty-five patients with histopathological confirmed PDAC are included, of which 35 are LN metastasis positive and 50 are LN metastasis negative. Initially, 1,124 radiomics features are computed from CT images of each patient. After a series of feature selection, a Radiomics logistic regression (LOG) model is developed. Subsequently, the predictive efficiency of the model is validated using a leave-one-out cross-validation method. The model performance is evaluated on discrimination and compared with the conventional CT evaluation method based on subjective CT image features. RESULTS Radiomics LOG model is developed based on eight most related radiomics features. Remarkable differences are demonstrated between patients with LN metastasis positive and LN metastasis negative in Radiomics LOG scores namely, 0.535±1.307 (mean±standard deviation) vs. -1.514±1.800 (mean±standard deviation) with p < 0.001. Radiomics LOG model shows significantly higher predictive efficiency compared to the conventional evaluation method of LN status in which areas under ROC curves are AUC = 0.841 with 95% confidence interval (CI: 0.758∼0.925) vs. AUC = 0.682 with (95% CI: 0.566∼0.798). Leave-one-out cross validation indicates that the Radiomics LOG model correctly classifies 70.3% cases, while the conventional CT evaluation method only correctly classifies 57.0% cases. CONCLUSION A radiomics-based strategy provides an individualized LN status evaluation in PDAC patients, which may help clinicians implement an optimal personalized patient treatment.
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Affiliation(s)
- Peng Liu
- Department of Radiology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Qianbiao Gu
- Department of Radiology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Xiaoli Hu
- Department of Radiology, First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xianzheng Tan
- Department of Radiology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Jianbin Liu
- Department of Radiology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - An Xie
- Department of Radiology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Feng Huang
- Department of Radiology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, China
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Liu C, Cheng H, Jin K, Fan Z, Gong Y, Qian Y, Deng S, Huang Q, Ni Q, Yu X, Luo G. Resected Pancreatic Cancer With N2 Node Involvement Is Refractory to Gemcitabine-Based Adjuvant Chemotherapy. Cancer Control 2020; 27:1073274820915947. [PMID: 32268796 PMCID: PMC7153189 DOI: 10.1177/1073274820915947] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 02/13/2020] [Accepted: 02/28/2020] [Indexed: 11/01/2022] Open
Abstract
Lymphatic metastasis is a major determinant of the outcome of resected pancreatic cancer. Gemcitabine-based adjuvant chemotherapy can improve the outcome of resected pancreatic cancer. However, the efficacy of gemcitabine against pancreatic cancer stratified by nodal involvement is unclear. In this study, patients who had undergone curative resection of pancreatic adenocarcinoma (612 cases) were included. The efficacy of adjuvant gemcitabine-based regimen, stratified by nodal status (negative, positive) or N substage (N0, no nodal involvement; N1, 1-3-node involvement; N2, ≥4-node involvement), was examined. Both the node-negative (hazard ratio [HR] = 0.62, 95% confidence interval [CI], 0.44-0.87, P = .006) and node-positive subgroups (HR = 0.45, 95% CI, 0.33-0.62, P < .001) benefited from gemcitabine-based adjuvant chemotherapy. Patients with N0 (ie, the node-negative subgroup) or N1 (HR = 0.36, 95% CI, 0.25-0.52, P < .001) disease benefited from gemcitabine-based chemotherapy. However, patients with N2 tumors (HR = 0.95, 95% CI, 0.50-1.78, P = .867) had poor response to gemcitabine-based treatment. Therefore, we postulate that resected pancreatic cancer with N2 node involvement is refractory to gemcitabine-based adjuvant chemotherapy. A more intensive adjuvant regimen may be required for N2 subgroup patients.
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Affiliation(s)
- Chen Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
- Authors contributed equally
| | - He Cheng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
- Authors contributed equally
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Zhiyao Fan
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Yitao Gong
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Yunzhen Qian
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Shengming Deng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Qiuyi Huang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Quanxing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
- Authors contributed equally
| | - Guopei Luo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, Shanghai, China
- Authors contributed equally
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